Autism Spectrum Disorder and Associated Factors in Children in Spain, 2017: Population-Based Cross-Sectional Study.

OBJECTIVES: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with biological, multicausal and polygenic origins. The true prevalence of ASD has not been clearly established. The aim of this study was to estimate the prevalence of ASD in children aged 3 to 14 years in Spain and to analyze the factors associated with it. METHODS: A cross-sectional observational study using data from the 2017 National Survey of Health in Minors in Spain. Primary outcome was the diagnosis of ASD, and sociodemographic, behavioral, health-related, the use of health services, household and medication use variables was analyzed. Multivariable logistic regression model with a correction for modelling rare events was fitted. Complex sampling was undertaken, using the survey elevation factor in the analysis. RESULTS: A total of 4409 children were included, and there were 26 children with ASD, for a prevalence of 0.59%, representing 29,143 children with ASD. Factors significantly associated were male sex, having visited a psychologist, and/or a speech therapist in the past year, presenting probable problems with peers, antisocial behavior, taking antibiotics and taking other medications. CONCLUSION: The findings of this study may be useful to inform health policies and develop strategic plans to identify and address the needs of children with ASD.

SIGNIFICANCE: Autism Spectrum Disorder are not as well researched as other more common health problems. This is due to several factors, including economic or logistics reasons such as the difficulty of having enough cases to investigate. We estimate that some 29,143 children. They were mostly boys, with more visits to psychologists and/or speech therapist, presenting probable problems with their peers, greater antisocial behavior and taking more antibiotics than children without ASD. Knowing the magnitude of this disorder, and the factors that are associated, can help to develop effective health policies, and develop health plans that can help people with this disorder.

Risk factors for low humoral response to BNT-162b2 in hemodialysis patients.

INTRODUCTION: Maintenance hemodialysis (HD) patients are at higher risk of both infection and mortality associated with the new SARS-CoV-2. Immunization through large-scale vaccination is the cornerstone of infection prevention in this population. This study aims to identify risk factors for low response to the BNT-162b2 (Pfizer BioNTech) vaccine in an HD cohort. MATERIALS AND METHODS: Observational prospective study of an HD group followed in a Portuguese Public Founded Hemodialysis Center who received BNT-162b2 vaccination. Specific anti-Spike IgG was evaluated as arbitrary units per milliliter (AU/mL) and compared against risk factors. RESULTS: Humoral response evaluated by IgG anti-Spike levels showed a strong correlation with Charlson comorbidity index (CCI) and intact parathormone (iPTH) after each inoculation (1st dose: rho = -0.64/0.54; 2nd dose: rho = -0.66/0.63, respectively; p < 0.01 throughout). After completing both doses: 1) no response (NR) was associated with female sex (p < 0.01), lower albumin and iPTH (p = 0.01); 2) weak response (WR) showed higher CCI, older age, lower iPTH, and lower albumin (p = < 0.01, p = 0.03, p < 0.01, p = 0.05, respectively). A binary regression model using CCI, sex (male), and central venous catheter (CVC) was statistically significant in prediction of WR after the 2nd dose with OR (95% CI): 1.81 (1.06 - 3.08); 0.05 (0.01 - 0.65); 13.55 (1.06 - 174.18), respectively (p = 0.01). CONCLUSION: Older age, higher CCI, lower iPTH and albumin as well as CVC as vascular access were associated with lower response to vaccination in our study. Comorbidity burden is suggested as a preferred indirect method to predict worst response when compared to age alone.

Better Anti-Spike IgG Antibody Response to SARS-CoV-2 Vaccine in Patients on Haemodiafiltration than on Haemodialysis.

INTRODUCTION: The antibody response to SARS-CoV-2 vaccine in haemodialysis (HD) patients is diminished compared to healthy subjects. The aim of this study was to compare the presence of reactive SARS-CoV-2 antibodies in patients with high-flux HD and on-line haemodiafiltration (HDF) three and 6 months after the second dose of SARS-CoV-2 vaccine since previous studies indicate that a sustained antibody response correlates with protection from disease. METHODS: We included 216 HD patients of which 157 had on-line HDF and 59 high-flux HD and 46 health care workers as controls and studied the presence of reactive anti-spike IgG antibodies three and 6 months after the second dose of SARS-CoV-2 vaccine. Clinical features between the patient groups were similar, but patients with on-line HDF had significantly higher Kt/V. RESULTS: The percentage of participants with reactive antibodies was significantly lower in patients compared to controls, both three and 6 months after the second dose of vaccine. Furthermore, the proportion of patients with reactive anti-spike IgG ≥1.0 6 months after the second dose of vaccine was significantly higher in patients with on-line HDF compared to in patients with high-flux HD. In logistic regression analyses adjusted for several clinical features, the variables associated with presence of reactive anti-spike IgG at 3 months after the second dose of vaccine were lower age, HDF treatment, not being obese and not having a previous solid organ transplant. The two variables with the strongest influence on the presence of reactive anti-spike IgG levels 6 months after the second dose of vaccine were treatment with on-line HDF and not having immunosuppressive therapy. CONCLUSION: This is the first study to show that on-line HDF preserves the antibody response better than high-flux HD after vaccination with SARS-CoV-2 vaccine. Treatment strategies that sustain the vaccine response are essential to apply in this vulnerable group of patients.

Peritoneal Dialysis Exit-Site Care Protocols in Portugal and Its Association with Catheter-Related Infections.

INTRODUCTION: Exit-site infection (ESi) prevention is a key factor in lowering the risk of peritonitis. This study aimed to evaluate the associations between exit-site (ES) care protocols and the annual incidence rates of ESi and peritonitis in Portugal. METHODS: We performed a national survey using two questionnaires: one about the incidence of catheter-related infections and the other characterizing patients' education and ES care protocols. RESULTS: In 2017 and 2018, 14 Portuguese units followed 764 and 689 patients. ESi incidence rate was 0.41 episodes/year, and the peritonitis incidence rate was 0.37. All units monitor catheter-related infections on a yearly basis, use antibiotic prophylaxis at the time of catheter placement, and treat nasal carriage of S. aureus, although with different approaches. Screening for nasal carriage of S. aureus is performed by 12 units, and daily topical antibiotic cream is recommended by 6 out of 14 of the units. We did not find statistical differences in ESi/peritonitis, comparing these practices. The rate of ESis was lower with nonocclusive dressing immediately after catheter insertion, bathing without ES dressing, with the use of colostomy bags in beach baths and was higher with the use of bath sponge. The peritonitis rate was lower with bathing without ES dressing and if shaving of the external cuff was performed in the presence of chronic ESi. CONCLUSIONS: We found potential proceedings associated with ESi and peritonitis. A regular national audit of peritoneal dialysis units is an important tool for clarifying the best procedures for reduction of catheter-related infections.

Higher daily temperature range at depth is linked with higher thermotolerance in antipatharians from the canary islands.

Sensitivity to ocean warming is generally expected to be lower in populations from more heterogeneous thermal environments, owing to greater phenotypic plasticity and/or genotype selection. While resilience of benthic populations from thermally fluctuating environments has been investigated at a variety of spatial scales, this has received limited attention across depths and has remained unresolved for Antipatharian corals, key habitat-forming species across a wide bathymetric range in all of the world oceans. In this study, we aimed at addressing the thermal sensitivity of Antipatharian corals across depths characterized by different levels of temperature fluctuations. We used an acute ramping experimental approach to compare the thermal sensitivity of colonies of (1) the branched Antipatharian Antipathella wollastoni (Gray, 1857) from two distinct depths (25 and 40 m) in Gran Canaria (Canary Islands, Spain); and of (2) unbranched mesophotic (80 m) Stichopathes species, from Lanzarote (Canary Islands, Spain; S. gracilis (Gray, 1857)), and Stichopathes sp. clade C from Mo'orea, French Polynesia. Results showed that the daily temperature range in Gran Canaria was larger at mesophotic depths (3.9 °C vs. 2.8 °C at 40 and 25 m, respectively) and this coincided with lower thermal sensitivity in mesophotic colonies of A. wollastoni. Second, S. gracilis from Lanzarote showed a lower thermal sensitivity than the previously studied Stichopathes sp. clade C from Mo'orea (French Polynesia) inhabiting a less variable habitat. These results are in line with the climate variability hypothesis, which states that populations under more variable thermal conditions have a lower sensitivity to warming than those from more stable environments, as they have adapted/acclimated to these higher levels of temperature fluctuations.

Partitioning resilience of a marine foundation species into resistance and recovery trajectories.

The resilience of an ecological unit encompasses resistance during adverse conditions and the capacity to recover. We adopted a 'resistance-recovery' framework to experimentally partition the resilience of a foundation species (the seagrass Cymodocea nodosa). The shoot abundances of nine seagrass meadows were followed before, during and after simulated light reduction conditions. We determined the significance of ecological, environmental and genetic drivers on seagrass resistance (% of shoots retained during the light deprivation treatments) and recovery (duration from the end of the perturbed state back to initial conditions). To identify whether seagrass recovery was linearly related to prior resistance, we then established the connection between trajectories of resistance and recovery. Finally, we assessed whether recovery patterns were affected by biological drivers (production of sexual products-seeds-and asexual propagation) at the meadow-scale. Resistance to shading significantly increased with the genetic diversity of the meadow and seagrass recovery was conditioned by initial resistance during shading. A threshold in resistance (here, at a ca. 70% of shoot abundances retained during the light deprivation treatments) denoted a critical point that considerably delays seagrass recovery if overpassed. Seed densities, but not rhizome elongation rates, were higher in meadows that exhibited large resistance and quick recovery, which correlated positively with meadow genetic diversity. Our results highlight the critical role of resistance to a disturbance for persistence of a marine foundation species. Estimation of critical trade-offs between seagrass resistance and recovery is a promising field of research to better manage impacts on seagrass meadows.

Insulin Resistance as a Diagnostic Criterion for Metabolically Healthy Obesity in Children.

OBJECTIVES: In recent years, a subgroup of individuals with obesity has been described as having a lower risk of metabolic and cardiovascular complications. These individuals have what is referred to as metabolically healthy obesity (MHO), which has a favorable metabolic profile and a lower probability of long-term complications. The definition of this subtype in children is not clear. The aim of the present study was to determine whether Homeostasis Model Assessment (HOMA) above a set threshold could be the marker of metabolically unhealthy obesity (MUO) in children, or a parameter that can be used in the overall assessment. It is intended to compare the International Diabetes Federation (IDF) criteria against HOMA in the diagnosis of MUO. METHODS: This observational, retrospective, cohort study included children with obesity and analyzed their metabolic state by means of blood testing and dual-energy X-ray absorptiometry. RESULTS: A total of 96 patients were included, 44.8% boys and 55.2% girls, ages 6-17 years. The patients with MHO according to the HOMA criterion were younger (P = 0.001), had a lower body mass index (BMI) z score (P = 0.006), waist-height index (P = 0.009), hip-height index (P = 0.010), blood glucose (P = 0.003), insulin (P < 0.001), and lower percentages of total fat (P = 0.002), trunk fat (P = 0.001), and android fat (P = 0.009) than those with MUO. The logistic regression analysis according to IDF criteria detected an area under the receiver operating characteristic (ROC) curve of 0.659 (95% CI 0.546-0.771; P = 0.009) versus the area under the ROC curve of 0.854 (95% CI 0.777-0.931; P < 0.001) for the HOMA definition. Therefore, the determination of the metabolic state according to HOMA has greater sensitivity and specificity than the IDF criteria. The multivariate analysis in children classified according to HOMA revealed that the percentage of total fat and gynoid fat distributions and triglyceride level could be markers of a healthy or unhealthy metabolic state in children with obesity (P < 0.001). CONCLUSIONS: The use of HOMA as a single criterion was demonstrated to be an effective and simple detector of adiposity, which predicts the metabolically healthy obesity in children.

Influence of weight status on bone mineral content measured by DXA in children.

INTRODUCTION: Childhood obesity is a public health problem with repercussions in later life. As tissue formation peaks in childhood we determined how weight status influences bone mineral content. MATERIAL AND METHODS: We studied 553 children aged 4-18 years over 10 years (46.8% girls). We measured age, weight, height and through bone densitometry (DXA), bone mineral content (BMC), bone mineral density (BMD), and waist, arm and hip circumferences. The patients were divided into groups using the body mass index z-score: underweight, normal weight, overweight, obese and very obese. RESULTS: BMC and BMD values were highest in the normal-weight and overweight groups. Logistic regression showed bone mineralization was inversely associated with waist circumference, the association being positive for weight and age. No differences were found according to sex. DISCUSSION: Studies of the relationship between weight and bone mineralization report contradictory results, often because of different study designs. Moreover, studies in children are either few or with small samples. Our findings in a large sample show the importance of weight status in bone mineralization given the risk of bone fractures or osteoporosis. CONCLUSIONS: Weight status influenced bone mineralization. BMC and BMD decreased in children with a higher degree of obesity. Waist circumference correlated negatively with bone mineralization.

Time-critical influences of gestational diet in a seahorse model of male pregnancy.

Sex role reversal is not uncommon in the animal kingdom but is taken to the extreme by the Syngnathidae, in which male pregnancy is one of the most astonishing idiosyncrasies. However, critical and time-dependent environmental effects on developing embryos, such as those extensively studied in mammalian pregnancy, have not been investigated in the male pregnancy context. Here, we tested the hypothesis that seahorse pregnancy is subject to 'critical windows' of environmental sensitivity by feeding male long-snouted seahorses (Hippocampus reidi) a diet deficient in polyunsaturated fatty acids during specific periods before and during pregnancy. Despite embryos being nourished principally by maternally supplied yolk, we found that offspring morphology, fatty acid composition and gene expression profiles were influenced by paternal diet in a manner that depended critically on the timing of manipulation. Specifically, reception of a diet deficient in polyunsaturated fatty acids in the days preceding pregnancy resulted in smaller newborn offspring, while the same diet administered towards the end of pregnancy resulted in substantial alterations to newborn gene expression and elongation of the snout at 10 days old. Although paternal diet did not affect 10 day survival, the observed morphological alterations in some cases could have important fitness consequences in the face of natural selective pressures such as predation and food availability. Our results demonstrate that, under male pregnancy, fine-scale temporal variation in parental diet quality and subsequent critical window effects should not be overlooked as determinants of developing offspring fitness.

Use of Eye-Tracking Technology by Medical Students Taking the Objective Structured Clinical Examination: Descriptive Study.

BACKGROUND: The objective structured clinical examination (OSCE) is a test used throughout Spain to evaluate the clinical competencies, decision making, problem solving, and other skills of sixth-year medical students. OBJECTIVE: The main goal of this study is to explore the possible applications and utility of portable eye-tracking systems in the setting of the OSCE, particularly questions associated with attention and engagement. METHODS: We used a portable Tobii Glasses 2 eye tracker, which allows real-time monitoring of where the students were looking and records the voice and ambient sounds. We then performed a qualitative and a quantitative analysis of the fields of vision and gaze points attracting attention as well as the visual itinerary. RESULTS: Eye-tracking technology was used in the OSCE with no major issues. This portable system was of the greatest value in the patient simulators and mannequin stations, where interaction with the simulated patient or areas of interest in the mannequin can be quantified. This technology proved useful to better identify the areas of interest in the medical images provided. CONCLUSIONS: Portable eye trackers offer the opportunity to improve the objective evaluation of candidates and the self-evaluation of the stations used as well as medical simulations by examiners. We suggest that this technology has enough resolution to identify where a student is looking at and could be useful for developing new approaches for evaluating specific aspects of clinical competencies.

A computational study of the vibrationally-resolved electronic circular dichroism spectra of single-chain transoid and cisoid oligothiophenes in chiral conformations.

We simulate the vibronic profile of the electronic circular dichroism (ECD) spectra of oligothiophenes in cisoid and transoid chiral arrangements. We consider oligomers of different lengths, from two to fifteen units, and investigate extensively how the ECD spectral shapes depend on the inter-ring torsions. In general, the molecular structures we consider are not stationary points of the ground state potential energy surface. Therefore, in order to perform vibronic calculations, we present a new computational protocol able to define reduced-dimensionality models where the effect of the off-equilibrium modes is removed. This is done adopting a description of the vibrational motions in curvilinear internal coordinates, and vertical harmonic models coupled with an iterative application of projectors to define energy Hessians, and therefore effective normal modes, in the space complementary to the one of the off-equilibrium coordinates. Although we consider both Franck-Condon and Herzberg-Teller contributions, the results show that transoid twisted ribbons always give rise to monosignated ECD spectra, while bi-signated and multi-signated spectra are expected for cisoid helices. These findings are explained on the basis of the different transition strengths of the lowest electronic states imparted by the different spatial arrangement, that is almost linear for transoid structures and more globular for cisoid ones. We predicted the chiroptical response of a large number of possible molecular arrangements. These data are employed to critically discuss the experimental ECD of polythiophenes in different experimental conditions, forming either aggregates or host-guest complexes. The method here proposed to perform vibronic calculations in reduced-dimensionality models is of general applicability and its potential interest goes beyond the practical application presented here.

Toward a general mixed quantum/classical method for the calculation of the vibronic ECD of a flexible dye molecule with different stable conformers: Revisiting the case of 2,2,2-trifluoro-anthrylethanol.

We extend a recently proposed mixed quantum/classical method for computing the vibronic electronic circular dichroism (ECD) spectrum of molecules with different conformers, to cases where more than one hindered rotation is present. The method generalizes the standard procedure, based on the simple Boltzmann average of the vibronic spectra of the stable conformers, and includes the contribution of structures that sample all the accessible conformational space. It is applied to the simulation of the ECD spectrum of (S)-2,2,2-trifluoroanthrylethanol, a molecule with easily interconvertible conformers, whose spectrum exhibits a pattern of alternating positive and negative vibronic peaks. Results are in very good agreement with experiment and show that spectra averaged over all the sampled conformational space can deviate significantly from the simple average of the contributions of the stable conformers. The present mixed quantum/classical method is able to capture the effect of the nonlinear dependence of the rotatory strength on the molecular structure and of the anharmonic couplings among the modes responsible for molecular flexibility. Despite its computational cost, the procedure is still affordable and promises to be useful in all cases where the ECD shape arises from a subtle balance between vibronic effects and conformational variety.

Application of electroencephalographic techniques to the study of visual impact of renewable energies.

Much is currently being studied on the negative visual impact associated to the installation of large wind turbines or photovoltaic farms. However, methodologies for quantitatively assessing landscape impact are scarce. In this work we used electroencephalographic (EEG) recordings to investigate the brain activity of 14 human volunteers when looking at the same landscapes with and without wind turbines, solar panels and nuclear power plants. Our results showed no significant differences for landscapes with solar power systems or without them, and the same happened for wind turbines, what was in agreement with their subjective scores. However, there were clear and significant differences when looking at landscapes with and without nuclear power plants. These differences were more pronounced around a time window of 376-407 msec and showed a clear right lateralization for the pictures containing nuclear power plants. Although more studies are still needed, these results suggest that EEG recordings can be a useful procedure for measuring visual impact.

Embryonic developmental plasticity in the long-snouted seahorse (Hippocampus reidi, Ginsburg 1933) in relation to parental preconception diet.

The aim of the present study was to investigate the hypothesis that parental periconception nutrition in adult seahorses affects the development and growth of their offspring. We tested the hypothesis that because seahorse embryos develop inside the male's brood pouch, manipulation of the male's diet would affect offspring growth and development independently of the female's diet. Adult males and females were fed separately with either wild-caught crustaceans or commercial aquarium diet for 1 month before conception to influence the periconception environment. Approximately 10000 offspring were obtained from four different treatment groups (Male/Wild or Male/Commercial×Female/Wild or Female/Commercial). Weights, physical dimensions and fatty acid profiles of the newborns were determined. Offspring produced when the males receiving commercial diet were mated with wild-fed females were larger (P<0.05) than those produced by wild-fed males. When both males and females were fed with commercial diet, their offspring were significantly smaller than those from the other treatment groups. When commercial diet-fed females were mated with wild-fed males, the offspring showed distortion of the snout:head length ratio. These results support the view that the preconception diet received by males and females differentially affects embryonic development.

Sexual selection and the adaptive evolution of PKDREJ protein in primates and rodents.

PKDREJ is a testis-specific protein thought to be located on the sperm surface. Functional studies in the mouse revealed that loss of PKDREJ has effects on sperm transport and the ability to undergo an induced acrosome reaction. Thus, PKDREJ has been considered a potential target of post-copulatory sexual selection in the form of sperm competition. Proteins involved in reproductive processes often show accelerated evolution. In many cases, this rapid divergence is promoted by positive selection which may be driven, at least in part, by post-copulatory sexual selection. We analysed the evolution of the PKDREJ protein in primates and rodents and assessed whether PKDREJ divergence is associated with testes mass relative to body mass, which is a reliable proxy of sperm competition levels. Evidence of an association between the evolutionary rate of the PKDREJ gene and testes mass relative to body mass was not found in primates. Among rodents, evidence of positive selection was detected in the Pkdrej gene in the family Cricetidae but not in Muridae. We then assessed whether Pkdrej divergence is associated with episodes of sperm competition in these families. We detected a positive significant correlation between the evolutionary rates of Pkdrej and testes mass relative to body mass in cricetids. These findings constitute the first evidence of post-copulatory sexual selection influencing the evolution of a protein that participates in the mechanisms regulating sperm transport and the acrosome reaction, strongly suggesting that positive selection may act on these fertilization steps, leading to advantages in situations of sperm competition.

Disentangling vibronic and solvent broadening effects in the absorption spectra of coumarin derivatives for dye sensitized solar cells.

We simulate from first-principles the absorption spectra of five structure-related coumarin derivatives utilized in dye sensitized solar cells (DSSCs), investigating the vibronic and solvent contributions to the position and width of the spectra in ethanol. Ground and excited state potential energy surfaces (PESs) are modeled by Density Functional Theory (DFT) and its time-dependent (TD) expression for the excited state (TD-DFT). The solute vibronic structure associated with the spectrum is calculated by a TD formalism, accounting for both Duschinsky and temperature effects, while solvent inhomogeneous broadening is evaluated according to Marcus' theory, computing the solvent reorganization energy by the state-specific implementation of the polarizable continuum model (PCM) within TD-DFT. We adopted both the standard hybrid PBE0 and the range separated CAM-B3LYP functionals showing that the latter performs better both concerning the vibronic and solvent-induced contributions to the absorption lineshape. The different predictions of the two functionals are then rationalized in terms of the charge transfer (CT) character of the transitions showing that, in this class of compounds, it is strongly dependent on the nuclear structure. Such a dependence introduces a bias in the PBE0 PES that has a drastic impact on the vibronic spectra. We show that both the intrinsic vibronic structure and the solvent broadening play a relevant role in differentiating the absorption width of the five dyes. In this sense, our results provide a guide to understand the sources of spectral broadening of this family of dyes, a valuable help for a rational design of new molecules to improve DSSC devices.

Absorption and emission spectral shapes of a prototype dye in water by combining classical/dynamical and quantum/static approaches.

We study the absorption and emission electronic spectra in an aqueous solution of N-methyl-6-oxyquinolinium betaine (MQ), an interesting dye characterized by a large change of polarity and H-bond ability between the ground (S0) and the excited (S1) states. To that end we compare alternative approaches based either on explicit solvent models and density functional theory (DFT)/molecular-mechanics (MM) calculations or on DFT calculations on clusters models embedded in a polarizable continuum (PCM). In the first approach (ClMD), the spectrum is computed according to the classical Franck-Condon principle, from the dispersion of the time-dependent (TD)-DFT vertical transitions at selected snapshots of molecular dynamics (MD) on the initial state. In the cluster model (Qst) the spectrum is simulated by computing the quantum vibronic structure, estimating the inhomogeneous broadening from state-specific TD-DFT/PCM solvent reorganization energies. While both approaches provide absorption and emission spectral shapes in nice agreement with experiment, the Stokes shift is perfectly reproduced by Qst calculations if S0 and S1 clusters are selected on the grounds of the MD trajectory. Furthermore, Qst spectra better fit the experimental line shape, mostly in absorption. Comparison of the predictions of the two approaches is very instructive: the positions of Qst and ClMD spectra are shifted due to the different solvent models and the ClMD spectra are narrower than the Qst ones, because MD underestimates the width of the vibrational density of states of the high-frequency modes coupled to the electronic transition. On the other hand, both Qst and ClMD approaches highlight that the solvent has multiple and potentially opposite effects on the spectral width, so that the broadening due to solute-solvent vibrations and electrostatic interaction with bulk solvent is (partially) counterbalanced by a narrowing of the contribution due to the solute vibrational modes. Qst analysis evidences a pure quantum broadening effect of the spectra in water due to vibronic progressions along the solute/solvent H-bonds.